The Mayo Clinic Study of Aging (MCSA) was established in 2004 as a population-based study of aging, mild cognitive impairment (MCI) and dementia in Olmsted County, MN. The specific aims were designed to estimate the population prevalence of normal cognition, MCI and its subtypes, to estimate incidence rates of MCI and dementia, and begin to explore predictors for these conditions. In the proposed renewal period, we plan to refine the incidence rates for MCI and dementia and to evaluate the utility of a variety of traditional and novel factors including medical comorbidities, biomarkers and imaging measures for predicting MCI and dementia. We propose the following specific aims: Specific Aim 1: To obtain stable estimates of incidence rates for normal cognition to MCI, its subtypes, and dementia, and its subtypes including Alzheimer's disease, and from MCI to dementia by sex and presumed etiology. Specific Aim 2: To investigate potential risk factors or predictors including clinical, biochemical and imaging markers for transitions from normal cognition to MCI and to dementia by sex and etiology, and from MCI to dementia by sex and etiology. Specific Aim 3: To explore multivariable models of risk factors or predictors resulting from Specific Aim 2 for transitions from normal cognition to MCI and dementia by sex and etiology and for MCI to dementia by subtypes and sex. Specific Aim 4: To provide subjects and biological materials for related research projects and provide a platform for training new investigators. To accomplish these goals, the current cohort will be replenished to 2000 persons (approximately 1650 cognitively normal and 350 MCI) by the time of the proposed grant initiation. We will use the Mayo Clinic medical records-linkage system to validate medical comorbidities and evaluate their role as predictors for our study outcomes. At the initiation of the proposed grant renewal period, we will have completed over 1500 quantitative MRI scans on the participants and will be in the process of obtaining cerebrospinal fluid and Pittsburgh Compound B scans on 600 persons randomly selected from the cohort. These measures will be combined with annual plasma A (3 measures and genotype information to develop multivariable prediction models. This proposed study will represent one of the first attempts to combine clinical, neuroimaging and biomarker information as predictors of cognitive impairment in a large non-demented population-based cohort over a period of 5 - 10 years. RELEVANCE (See instructions): We urgently need techniques to predict which individuals will develop mild cognitive impairment and Alzheimer's disease (AD) in the future. The Mayo Clinic Study of Aging is designed to explore the utility of common and novel medical risk factors, neuroimaging measures and biomarkers to predict AD in a population-based setting. This information is essential for public health purposes and for the planning of clinical trials for the prevention of AD.